Is DSCAM p.Ala788Val (c.2363C>T) pathogenic?

DSCAM p.Ala788Val (c.2363C>T) is classified Likely pathogenic in DSCAM (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.7238); Very rare (popmax 0.0012%, sas); Associated with Hirschsprung disease.

What condition is associated with DSCAM p.Ala788Val (c.2363C>T)?

DSCAM p.Ala788Val (c.2363C>T) is associated with Hirschsprung disease (ClinVar).

How common is DSCAM p.Ala788Val (c.2363C>T) in the general population?

DSCAM p.Ala788Val (c.2363C>T) is very rare (popmax 0.0012%, sas) (gnomAD).

How is Hirschsprung disease inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DSCAM p.Ala788Val (c.2363C>T)?

AlphaMissense predicts likely pathogenic (score 0.7238) — an in-silico prediction, not a clinical call.

DSCAM p.Ala788Val

c.2363C>T · rs1419539530 · VCV599423

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7238 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0012%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Hirschsprung disease

Computational evidence

Protein change
AlphaMissense	0.7238	likely pathogenic ✓ concordant with ClinVar
REVEL	0.271	benign-leaning
SaProt	LLR -9.41	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 149 kb · p 1.9e-14 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0012% South Asian · 1/83,640 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000573% 9/1,570,026 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00795%	12,582
Remaining individualsnot grpmax-eligible	0.00165%	60,442
South Asiangrpmax	0.0012%	83,640
European (non-Finnish)	0.000172%	580,494

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DSCAM
Protein: p.Ala788Val
Coding: c.2363C>T
MANE Select: NM_001389
dbSNP: rs1419539530
Type: single nucleotide variant
Location: chr21:40189232 (GRCh38)
Gene constraint: LOEUF 0.28 · pLI 1.00 · ClinGen HI 2/3 (gnomAD)
Structure: AlphaFold pLDDT 69.98 · 1 PDB
Residue 788: the ig-like c2-type 9 domain

Full DSCAM gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Hirschsprung disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hirschsprung disease (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Multigenic/multifactorial
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

DSCAM p.Ala788= Likely benign ★ same residue
DSCAM p.Ser682Arg Uncertain significance ★★ ⚠ same type
DSCAM c.5383+9T>A Benign ★★ same type
DSCAM p.Ala153= Benign ★★ same type
DSCAM p.Arg1798= Benign/Likely benign ★★ same type
DSCAM p.Asn1250= Benign ★★ same type
DSCAM p.Asn576= Benign/Likely benign ★★ same type
DSCAM p.Asp185= Benign/Likely benign ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dscam-p-ala788val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown